Immune System
Immune System
Immune System
2. Innate Immunity
Innate immunity is accomplished by mechanical mechanisms, chemical mediators, cells, and the
inflammatory response.
Mechanical Mechanisms
The skin and mucous membranes form barriers that prevent the entry of microorganisms into the body.
Tears, saliva, and urine act to wash away microorganisms from the surfaces of the body.
Chemical Mediators are molecules responsible for many aspects of innate immunity. Some chemical that are
found on the surface of the cells kill microorganisms or prevent their entry into the cells. Lysozyme in tears and
saliva kills certain bacteria, and mucus on mucous membranes prevent the entry of some microorganisms.
Other chemical mediators, such as histamine, complement, prostaglandins, and leukotrienes, promote
inflammation by causing vasodilation, increasing vascular permeability, and stimulating phagocytosis. In
addition, interferons protect cells against viral infections.
Cells
White blood cells and the cells derived from white blood cells are the most important cellular components of
immunity. White blood cells are produced in red bone marrow and lymphatic tissue and are released into the
blood. Chemicals released from microorganisms or damaged tissues attract the white blood cells, and they
leave the blood and enter affected tissues. Important chemicals known to attract white blood cells include
complement, leukotrienes, kinins, and histamine. The movement of white blood cells toward these chemicals
is called chemotaxis.
Phagocytic Cells: Phagocytosis is the ingestion and destruction of particles by cells called phagocytes. The
particles can be microorganisms or their parts, foreign substances, or dead cells from the individual’s body.
The most important phagocytes are neutrophils and macrophages, although other white blood cells also
have limited phagocytic ability. Neutrophils are small phagocytic cells that are usually the first cells to enter
infected tissues from the blood in large numbers; however, neutrophils often die after phagocytizing a single
microorganism. Pus is an accumulation of fluid, dead neutrophils, and other cells at a site of infection.
Macrophages are monocytes that leave the blood, enter tissues, and enlarge about fivefold. Monocytes and
macrophages form the mononuclear phagocytic system because they phagocytes with a single (mono),
unlobed nucleus. Sometimes macrophages are given specific names such as dust cells in the lungs, Kupffer
cells in the liver, and microglia in the central nervous system. Macrophages can ingest more and larger items
than can neutrophils. Macrophages usually appear in infected tissues after neutrophils and are responsible for
most of the phagocytic activity in the late stages of infection, including the cleanup of dead neutrophils and
other cellular debris.
Cells of Inflammation: Basophils, which are derived from red bone marrow, are motile white blood cells that
can leave the blood and enter infected tissues. Mast cells, which are also derived from red bone marrow, are
nonmotile cells in connective tissue, especially near capillaries. Like macrophages, mast cells are locate at
potential points of entry for microorganisms into the body such as the skin, lungs, gastrointestinal tract, and
urogenital tract. Basophils and mast cells can be activated through innate immunity (by complement) or
through adaptive immunity. When activated, they release chemicals such as histamine and leukotrienes that
produce an inflammatory response or activate other mechanisms such as smooth muscle contraction in the
lungs. Eosinophils are produced in red bone marrow, enter the blood, and within a few minutes enter tissues.
Enzymes released by eosinophils break down chemicals released by basophils and mast cells. Thus at the
same time that inflammation is initiated, mechanisms are activated that contain and reduce the
inflammatory response.
Natural Killer Cells: Natural Killer (NK) cells are type of lymphocyte produced in red bone marrow, and they
account for up to 15% of lymphocytes. NK cells recognize classes of cells, such as tumor cells or virus-infected
cells in general, rather than the specific tumor cells or cells infected by a specific virus. For this reason, and
because NK cells do not exhibit a memory response, NK cells are classified as part of innate immunity. NK cells
use a variety of methods to kill their target cells, including the release of chemicals that damage cell
membranes, causing cells to lyse.
Inflammatory Response
Chemical mediators cause vasodilation and increase vascular permeability, allowing the entry of chemicals
into damaged tissues. Chemicals also attract phagocytes.
The amount of chemical mediators and phagocytes increases until the cause of the inflammation is
destroyed. Then the tissues undergo repair.
Local inflammation produces the symptoms of redness, heat, swelling, pain, and loss of function. Symptoms of
systemic inflammation include an increase in neutrophil numbers, fever, and shock.
3. Adaptive Immunity
Adaptive immunity exhibits specificity and memory. Specificity is the ability to recognize substance, and
memory is the ability to respond with increasing effectiveness to successive exposure to antigen. Substances
that stimulate adaptive immune responses are called antigens.
B cells are responsible for humoral, or antibody-mediated, immunity. T cells are involved with cell-mediated
immunity.
Origin and Development of Lymphocytes
B and T cells originate in red bone marrow. T cells are processed in the thymus and B cells are processed in
red bone marrow.
B and T cells move to lymphatic tissue from their processing sites. They continually circulate from one
lymphatic tissue to another.
Activation and Multiplication of Lymphocytes
B cells and T cells have antigen receptors on their surfaces. Clones are lymphocytes with the same antigen
receptor.
Major histocompatibility complex (MHC) molecules present processed antigens to B or T cells.
Costimulation by cytokines, such as interleukins, and surface molecules, such as CD4, are required in addition
to MHC molecules.
Macrophages present processed antigens to helper T cells, which divide and increase in number.
Helper T cells stimulate B cells to divide and differentiate into cells that produce antibodies.
Antibody-Mediated Immunity
Antibodies are proteins. The variable region combines with antigens and is responsible for antibody
specificity. The constant region activates complement or attaches the antibody to cells. The five classes of
antibodies are IgG, IgM, IgA, IgE, and IgD.
Antibodies directly inactivate antigens or cause them to clump together. Antibodies indirectly destroy
antigens by promoting phagocytosis and inflammation.
The primary response results from the first exposure to an antigen. B cells form plasma cells, which produce
antibodies, and memory B cells.
The secondary (memory) response results from exposure to an antigen after primary response. Memory B cells
quickly form plasma cells and new memory B cells.
Effects of Antibodies
Antibodies directly affect antigens by inactivating the antigens or binding the antigens together. Antibodies
indirectly affect antigens by activating other mechanisms through the constant region of the antibody.
Indirect mechanisms include activation of complement, increased inflammation resulting from the release of
inflammatory chemicals from mast cells or basophils, and increased phagocytosis resulting from antibody
attachment to macrophages.
Inflammation is important in activating the adaptive immune response (acts as danger signals for the body).
Therefore, stopping inflammation is not always a good thing. For example, you need to have a fever to really
mount a full-blown response against a pathogen so taking paracetamol when you have a mild fever (below
38.3 C) for example, may not always be a good thing since you may lose the sterilizing effects of the fever
and dampen the danger signals that activate the adaptive immune response. However, it is still best to get
medical advice on how to treat disease.
Acute inflammation can be good since it activates the immune response, but chronic inflammation (e.g.,
arthritis, psoriasis, irritable bowel disease) is bad because it ultimately leads to tissue damage.
The antibody response is best suited to combat pathogens that survive outside of the cell, such as bacteria,
fungi, and some worms.
Drugs and other therapeutic agents can be attached to antibodies that are specific for antigens on cancer
cells. This allows for specific targeting of these drugs to the diseased cells, thereby avoiding damage to
healthy tissue.
The adaptive immune response is activated by the presence of foreign substances (proteins, nucleic acids,
sugars, etc. found on pathogens).
Although it is important to turn on the immune response during an infection, it is just as important that it is
turned off after the infection is gone.
Most vaccines today contain an adjuvant (substance that activates the innate immune response) along with
a protein antigen from the pathogen, or an inactivated version of the pathogen which stimulates B cells to
produce antibodies against the pathogen. After getting the vaccine, you now have cells that remember the
pathogen and can act quickly when you actually get infected with the disease-causing organism. This
memory of the B cells and quick response prevents the person from feeling any symptoms of the disease.
Cell-Mediated Immunity
Exposure to antigen activates cytotoxic T cells and produces memory T cells.
Cytotoxic T cells lyse virus-infected cells, tumor cells, and tissue transplants. Cytotoxic T cells produce
cytokines, which promote inflammation and phagocytosis.
There are 3 major types of T cells: cytotoxic T cells, helper T cells and regulatory T cells.
A. Cytotoxic T cells recognize virus-infected cells and kill them.
B. Helper T cells secrete proteins that help other immune cells (B cells, macrophages, etc.) survive and
perform their function.
C. Regulatory T cells control the immune response by turning it off. This prevents the immune system from
harming the body.
T cells have to recognize the foreign antigen in the context of a self- molecule, the MHC molecule. This
ensures that the immune system will only be activated when there is a real infection in the body.
It is important to only activate the T cell response (particularly the cytotoxic and helper T response) only if
there is a real infection because these responses are very potent and could potentially harm the body if they
are not regulated properly.
Regulatory T cells are very important because loss in their function can lead to autoimmune disease. This
occurs when the immune system starts to attack itself.
4. Acquired Immunity
Active natural immunity results from everyday exposure to an antigen against which the person’s own
immune system mounts a response.
Active artificial immunity results from deliberate exposure to an antigen (vaccine) to which the person’s own
immune system responds.
Passive natural immunity is the transfer of antibodies from a mother to her fetus during gestation or baby
during breastfeeding.
Passive artificial immunity is the transfer of antibodies from an animal or another person to a person requiring
immunity.
Antiserum is the general term used for antibodies that provide passive artificial immunity because the
antibodies are found in serum, which is plasma minus the clotting factors. Antisera are available against
microorganisms that cause disease such as rabies, hepatitis, and measles; bacterial toxins such as tetanus,
diphtheria, and botulism; and venoms from poisonous snakes and spiders.